Familial Mediterranean fever (FMF) is an autosomal recessive disease frequently seen in non-Ashkenazi Jews, Arabs, Armenians, and Turks. The main clinical features include periodic attacks of fever and serositis, sometimes complicated with amyloidosis. The underlying molecular defect is unknown. After the FMF gene (designated MEF) was mapped to 16p13, an international consortium was formed by the laboratories listed above to facilitate the cloning of the MEF gene. Genetic mapping by the consortium has localized MEF to an 1 cM interval. A cosmid contig has been constructed for the critical region. Additional genetic analysis has placed the gene to an interval of about 250 kb. Multiple efforts has been launched by the consortium to identify transcribed genes in the region, and to detect disease-causing mutations in those genes. Our group used a sequencing strategy to identify transcribed genes. Ten cosmids in the region were sequenced to obtain about 40 kb sequences each, and the sequences were analyzed to identify genes by BLASTN, BLASTX, and GRAIL. Many gene fragments or exons have been identified this way, in excellent agreement with genes isolated by other methodologies. Mutation detection by SSCP and direct sequencing is in progress.